The activation and regulation of the plant immune system requires the coordinated function of numerous pre-formed and inducible cellular responses. Following pathogen perception, plants not only activate specific defense-associated signaling, such as resistance (R) genes, but also redirect basic cellular machinery to support innate immune signaling. Within each of these processes, the actin cytoskeleton has been demonstrated to play a significant role in structural-based defense signaling in plants in response to pathogen infection. Most notably, the actin cytoskeleton of plants has been shown to play a role in structural-based defense signaling following fungal pathogen infection. Recent work from our laboratory has demonstrated that the actin cytoskeleton of Arabidopsis mediates defense signaling following perception of the phytopathogenic bacterium Pseudomonas syringae. Using a combination of genetic and cell biology-based approaches, we found that ADF4, a regulator of actin cytoskeletal dynamics, is required for the specific activation of R-gene-mediated signaling. By analyzing the activation of signaling following pathogen perception, we have identified substantial crosstalk between recognition of pathogen virulence factors (e.g., effector proteins) and the regulation of R-gene transcription. In total, our work highlights the intimate relationship between basic cellular processes and the perception and activation of defense signaling following pathogen infection.